Legumain was discovered in 1993 in plants, where the enzyme is present in legumes and in seeds of other plants. Then legumain was cloned, isolated and characterized from different species, e.g. from mouse, and from pig kidney. Human legumain was characterized after over-expression in a murine cell line.
The catalytic dyad is found in the motif His-Gly-spacer-Ala-Cys, and was confirmed by si-directed mutagenesis. Due to the presence of the same motif in caspases, clostripain, gingipain and separase these proteases where classified as Clan CD. Legumain is inhibited by iodoacetamid, maleimides, and ovocystatin, but is unaffected by E64.
Mammalian legumain is a lysosomal enzyme being highly specific for post-asparagine cleavage. It has been shown that the cleavage is inhibited by the glycosylation of the P1-asparagine residue. Furthermore, it is involved in the processing of antigens for the class II MHC presentation.
Different isoforms of legumain were purified from a plant source (seeds of kidney bean, Phaseolus vulgaris) and a mammal (kidney of pig, Sus scropha).
Autoimmune Reactions
Sometimes the immune system malfunctions, misinterprets the body's tissues as foreign, and attacks them, resulting in an autoimmune reaction. Autoimmune reactions can be triggered in several ways:
A substance in the body that is normally strictly contained in a specific area (and thus is hidden from the immune system) is released into the general circulation. For example, the fluid in the eyeball is normally contained within the eyeball's chambers. If a blow to the eye releases this fluid into the bloodstream, the immune system may react against it. A normal body substance is altered. For example, viruses, drugs, sunlight, or radiation may change a protein's structure in a way that makes it seem foreign. The immune system responds to a foreign substance that is similar in appearance to a natural body substance and inadvertently targets the body substance as well as the foreign substance. Something malfunctions in the cells that control antibody production. For example, cancerous B lymphocytes may produce abnormal antibodies that attack red blood cells. The results of an autoimmune reaction vary. Fever is common. Various tissues may be destroyed, such as blood vessels, cartilage, and skin. Virtually any organ can be attacked by the immune system, including the kidneys, lungs, heart, and brain. The resulting inflammation and tissue damage can cause kidney failure, breathing problems, abnormal heart function, pain, deformity, delirium, and death.
A large number of disorders almost certainly have an autoimmune cause, including lupus (systemic lupus erythematosus), myasthenia gravis, Graves' disease, Hashimoto's thyroiditis, pemphigus, rheumatoid arthritis, scleroderma, Sjögren's syndrome, pernicious anemia, multiple sclerosis and type I diabetes.
Immune diseases include but are not limited to conditions involving T-cells and/or macrophages such as acute and delayed hypersensitivity, graft rejection and graft-versus-host disease.